Upregulation of Claudin-7 Expression by Angiotensin II in Colonic Epithelial Cells of Mice Fed with NaCl-Depleted Diets
Dietary NaCl depletion increases Na<sup>+</sup> and Cl<sup>−</sup> absorption in the colon, but the mechanisms are not fully understood. So far, we reported that the expression of claudin-7 (CLDN7), a tight junction (TJ) protein, was upregulated in the mice fed with...
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MDPI AG
2020-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/4/1442 |
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| author | Yui Takashina Noriko Ishizuka Naotaka Ikumi Hisayoshi Hayashi Aya Manabe Chieko Hirota Yoshiaki Tabuchi Toshiyuki Matsunaga Akira Ikari |
| author_facet | Yui Takashina Noriko Ishizuka Naotaka Ikumi Hisayoshi Hayashi Aya Manabe Chieko Hirota Yoshiaki Tabuchi Toshiyuki Matsunaga Akira Ikari |
| author_sort | Yui Takashina |
| collection | DOAJ |
| description | Dietary NaCl depletion increases Na<sup>+</sup> and Cl<sup>−</sup> absorption in the colon, but the mechanisms are not fully understood. So far, we reported that the expression of claudin-7 (CLDN7), a tight junction (TJ) protein, was upregulated in the mice fed with NaCl-depleted diets, but the regulatory mechanism has not been clarified. Here, we found that angiotensin II (ANGII) increases the mRNA level of CLDN7, which was inhibited by losartan, a type 1 ANGII (AT1) receptor antagonist. Immunofluorescence measurement showed that CLDN7 is colocalized with zonula occludens-1 at the TJ in untreated and ANGII-treated cells. ANGII decreased transepithelial electrical resistance (TER) and increased permeability to C1<sup>−</sup> without affecting permeability to lucifer yellow, a paracellular flux marker. In contrast, TER was increased by CLDN7 knockdown in the absence and presence of ANGII. ANGII increased the nuclear distribution of phosphorylated p65 subunit of NF-κB, which was inhibited by losartan. The ANGII-induced elevation of CLDN7 expression was blocked by BAY 11-7082 (BAY), an NF-κB inhibitor. Luciferase reporter assay showed that ANGII increases promoter activity of CLDN7, which was inhibited by the treatment with losartan or BAY, and introduction of mutations in κB-binding motifs in the promoter. The binding of p65 on the promoter region of CLDN7 was increased by ANGII, which was inhibited by losartan and BAY in chromatin immunoprecipitation assay. Our data suggest that ANGII acts on AT1 receptor and increases paracellular permeability to Cl<sup>−</sup> mediated by the elevation of CLDN7 expression in the colon. |
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| language | English |
| last_indexed | 2024-04-13T11:35:38Z |
| publishDate | 2020-02-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c58ffc3296884527a7843cd17d17c28f2022-12-22T02:48:27ZengMDPI AGInternational Journal of Molecular Sciences1422-00672020-02-01214144210.3390/ijms21041442ijms21041442Upregulation of Claudin-7 Expression by Angiotensin II in Colonic Epithelial Cells of Mice Fed with NaCl-Depleted DietsYui Takashina0Noriko Ishizuka1Naotaka Ikumi2Hisayoshi Hayashi3Aya Manabe4Chieko Hirota5Yoshiaki Tabuchi6Toshiyuki Matsunaga7Akira Ikari8Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Gifu 501-1196, JapanSchool of Food and Nutritional Sciences, University of Shizuoka, Shizuoka 422-8526, JapanSchool of Food and Nutritional Sciences, University of Shizuoka, Shizuoka 422-8526, JapanSchool of Food and Nutritional Sciences, University of Shizuoka, Shizuoka 422-8526, JapanLaboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Gifu 501-1196, JapanLaboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Gifu 501-1196, JapanLife Science Research Center, University of Toyama, Toyama 930-0194, JapanEducation Center of Green Pharmaceutical Sciences, Gifu Pharmaceutica, University, Gifu 502-8585, JapanLaboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Gifu 501-1196, JapanDietary NaCl depletion increases Na<sup>+</sup> and Cl<sup>−</sup> absorption in the colon, but the mechanisms are not fully understood. So far, we reported that the expression of claudin-7 (CLDN7), a tight junction (TJ) protein, was upregulated in the mice fed with NaCl-depleted diets, but the regulatory mechanism has not been clarified. Here, we found that angiotensin II (ANGII) increases the mRNA level of CLDN7, which was inhibited by losartan, a type 1 ANGII (AT1) receptor antagonist. Immunofluorescence measurement showed that CLDN7 is colocalized with zonula occludens-1 at the TJ in untreated and ANGII-treated cells. ANGII decreased transepithelial electrical resistance (TER) and increased permeability to C1<sup>−</sup> without affecting permeability to lucifer yellow, a paracellular flux marker. In contrast, TER was increased by CLDN7 knockdown in the absence and presence of ANGII. ANGII increased the nuclear distribution of phosphorylated p65 subunit of NF-κB, which was inhibited by losartan. The ANGII-induced elevation of CLDN7 expression was blocked by BAY 11-7082 (BAY), an NF-κB inhibitor. Luciferase reporter assay showed that ANGII increases promoter activity of CLDN7, which was inhibited by the treatment with losartan or BAY, and introduction of mutations in κB-binding motifs in the promoter. The binding of p65 on the promoter region of CLDN7 was increased by ANGII, which was inhibited by losartan and BAY in chromatin immunoprecipitation assay. Our data suggest that ANGII acts on AT1 receptor and increases paracellular permeability to Cl<sup>−</sup> mediated by the elevation of CLDN7 expression in the colon.https://www.mdpi.com/1422-0067/21/4/1442colonclaudin-7angiotensin ii |
| spellingShingle | Yui Takashina Noriko Ishizuka Naotaka Ikumi Hisayoshi Hayashi Aya Manabe Chieko Hirota Yoshiaki Tabuchi Toshiyuki Matsunaga Akira Ikari Upregulation of Claudin-7 Expression by Angiotensin II in Colonic Epithelial Cells of Mice Fed with NaCl-Depleted Diets International Journal of Molecular Sciences colon claudin-7 angiotensin ii |
| title | Upregulation of Claudin-7 Expression by Angiotensin II in Colonic Epithelial Cells of Mice Fed with NaCl-Depleted Diets |
| title_full | Upregulation of Claudin-7 Expression by Angiotensin II in Colonic Epithelial Cells of Mice Fed with NaCl-Depleted Diets |
| title_fullStr | Upregulation of Claudin-7 Expression by Angiotensin II in Colonic Epithelial Cells of Mice Fed with NaCl-Depleted Diets |
| title_full_unstemmed | Upregulation of Claudin-7 Expression by Angiotensin II in Colonic Epithelial Cells of Mice Fed with NaCl-Depleted Diets |
| title_short | Upregulation of Claudin-7 Expression by Angiotensin II in Colonic Epithelial Cells of Mice Fed with NaCl-Depleted Diets |
| title_sort | upregulation of claudin 7 expression by angiotensin ii in colonic epithelial cells of mice fed with nacl depleted diets |
| topic | colon claudin-7 angiotensin ii |
| url | https://www.mdpi.com/1422-0067/21/4/1442 |
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